MTT is a malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. In 1938, Masson and Martin first described this compound tumor. They proposed that this tumor induces skeletal muscle differentiation in the same way as normal nerves (1). It got the name as malignant salamander tumor in 1973, basing on previous observations that if the sciatic nerve was implanted into the dorsal side, the salamander would produce redundant limbs composed of striated muscle, bone and nerve tissue. They mimic other brain tumors on MRI, which brings challenges to preoperative diagnosis. This the first MTT case reported with concomitant pituitary adenoma in the sellar area.

MTTs is a subgroup of malignant peripheral nerve sheath tumors (MPNST), which are reported to exhibit rhabdomyosarcoma-like differentiation and follow a particularly aggressive course (5). Due to the rarity of MTT, merely eleven intracranial cases have been reported, which is summarized in Table 1. To the best of our knowledge, the present case is the first report of MTT in sellar region with a clear history of radiation and a concurrent relapsed pituitary adenoma.

It is generally believed that the striated muscle cells in tumors are induced by or directly transformed from Schwann cells (6). In the present case, the visual acuity of the patient recovered completely after operation and the MTT component located apart from the optic nerve, which can basically exclude the origination of MTT from the optic nerve sheath.

MTTs mimic gliomas on MRI (7), where both of them show irregular masses, fuzzy boundaries, a peripheral increase, a low or equal signal on T1, and a high signal on T2 images (8). Genomic and proteomic studies have begun to reveal the complexity of chromosome and transcriptional changes behind these tumors, but reliable cytogenetic markers have not been established to distinguish MTT and MPNST and/or explain the obvious differences in their behavior (9–11). Daimaru et al. proposed a relatively widely accepted definition, including the following (12): (1) The first criterion is that, it is shown as a malignant schwannoma under the microscope and contains focal rhabdomyoblasts; The second criterion is that, the tumor is mainly composed of striated muscle and focal Schwann cells, which are found in neuropathy or NF-1 expression. Now, the diagnosis of MTT commonly depended on these criteria and on immunohistochemical findings (13).

The differential diagnosis of MTT includes other spindle cell malignant tumors, such as fibrosarcoma, synovial monophase sarcoma, leiomyosarcoma, low-grade fibroblast sarcoma, especially spindle cell rhabdomyosarcoma (14). Low-grade myofibroblastic sarcomas, synovial sarcomas, and fibrosarcomas do not contain rhabdomyoblasts and do not respond to skeletal muscle staining such as Desmin. Rhabdomyosarcoma, especially embryonic rhabdomyosarcoma, is mainly consisted of undifferentiated round cells and spindle cells (15). However, the composition of rhabdomyosarcoma is different from that of MTT, and the mean age of patients with rhabdomyosarcoma is younger than the patients with MTTs. In addition, there are usually high-density cell areas surrounding blood vessels, alternating with parvicellular areas rich in mucosal intercellular material.

In the present case, immunostainings were positive for skeletal muscle markers including Myogenin, Desmin, and Myod1, which supports the diagnosis. Interestingly, TTF-1 immunoreactivity was observed in the MTT component. Given that TTF-1 could be found in 66.7% of schwannomas (2), this result also supported the diagnosis of MTT. Moreover, in the 2017 WHO classification of pituitary tumors (4), TTF-1 expressing pituitary tumors of the posterior lobe represent a morphological spectrum of a single nosological entity. Considering the location of the tumor in our present case, we boldly speculate that there is possibility that MTT portion might arise from the mesodermal components in the posterior lobe of pituitary gland. Additionally, S100 protein is immunopositive in 50%–90% of MPNSTs (13), while S100 protein was negative in our case. We hypothesize that it might be explained by the following reasons: (1) the MTT tissue in our present case was not fully differentiated to express S100; (2) the S100-positive tissue was discarded or vacuumed during the surgical operation and was not provided for pathological examination.

It is reported that 8% of patients with MTT had been exposed to radiation, which is recognized as a risk factor (16–18). In addition, even therapeutic radiation can trigger the formation of MTT (19). Our report also provides evidence that the occurrence of MTT might be induced by radiation therapy.

Since MTT is rare and lack of prospective clinical trials, there is no standard treatment available. The 5-year survival rate of patients with MTT was 11%–14%, which was significantly lower than those patients with MPNST (34%–52%) (13, 14, 16). The adverse prognostic factors of MTTS mainly include NF-1, age, size, surgical method, positive surgical margin, early local recurrence, and the location of the tumor in the trunk (19).

Complete resection can improve the prognosis, reduce the risk of local recurrence and metastasis, and improve the efficacy of adjuvant therapy. In contrast, subtotal cytoreductive surgery cannot improve the survival rate of MTT patients (13). Adjuvant radiation therapy reduces the risk of death, but is not associated with a reduction in progression or recurrence (16). Although adjuvant chemotherapy has not been proved to be effective (16), there are certain evidence that patients who respond to neoadjuvant chemotherapy should also receive adjuvant therapy immediately (20). However, most MTT patients usually die within a few months, even after receiving optimal treatments (18).

In the future, we hope to have more cases and studies to better understand this tumor and provide more reliable diagnostic methods, especially pathological diagnostic criteria and more effective treatment strategies.

In summary, to our knowledge, this is the first report of MTT in sellar region with concurrent other tumors. This case had a history of radiation exposure after the first operation, which suggests that the occurrence of MTT might be caused by radiation. The patient received partial resection of the lesion with a transnasal transsphenoidal approach. The patient did not receive any adjuvant treatment postoperatively. Eventually, he died 64 days after the operation. Unfortunately, due to the rapid progress of the patient's condition, this case did not have much value for reference in treatment. In the future, we hope to have more cases and studies to better understand this tumor and provide more reliable diagnostic methods, especially pathological diagnostic criteria and more effective treatment strategies.